A novel estrogen receptor α-associated protein, template-activating factor Iβ, inhibits acetylation and transactivation

Margaret A. Loven, Nemone Muster, John R. Yates, Ann M. Nardulli

Research output: Contribution to journalArticle

Abstract

Estrogen receptor-α (ERα) functions as a ligand-activated transcription factor that alters expression of estrogen-responsive genes in target cells. Numerous regulatory proteins interact with ERα to influence estrogen-mediated transactivation. We have identified a novel coregulatory protein, template-activating factor-Iβ (TAF-Iβ), which binds to ERα in vitro when the receptor is not complexed with an estrogen response element. The central region of TAF-Iβ interacts with both the DNA-binding domain and the carboxy-terminal region of ERα. Coimmunoprecipitation experiments demonstrate that TAF-Iβ is associated with the unoccupied, but not the estrogen-occupied, ERα in MCF-7 breast cancer cells. Overexpression of TAF-Iβ inhibits ERα-mediated transcription in a dose-dependent manner. TAF-Iβ represses p300-mediated acetylation of histones and ERα in vitro and decreases ERα acetylation in vivo. TAF-Iβ also binds to other nuclear receptor superfamily members and represses thyroid hormone receptor β-induced transcription in transient transfection assays. Taken together, these data provide evidence that TAF-Iβ regulates transcription of estrogen-responsive genes by modulating acetylation of histones and ERα and that the effects of TAF-Iβ extend to other nuclear receptor superfamily members as well.

Original languageEnglish (US)
Pages (from-to)67-78
Number of pages12
JournalMolecular Endocrinology
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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